A Combined Treatment of BMP2 and Soluble VEGFR1 for the Enhancement of Tendon-Bone Healing by Regulating Injury-Activated Skeletal Stem Cell Lineage.

BACKGROUND: Bone morphogenetic protein 2 (BMP2) is an appealing osteogenic and chondrogenic growth factor for promoting tendon-bone healing. Recently, it has been reported that soluble vascular endothelial growth factor (VEGF) receptor 1 (sVEGFR1) (a VEGF receptor antagonist) could enhance BMP2-induced bone repair and cartilage regeneration; thus, their combined application may represent a promising treatment to improve tendon-bone healing. Moreover, BMP2 could stimulate skeletal stem cell (SSC) expansion and formation, which is responsible for wounded tendon-bone interface repair. However, whether the codelivery of BMP2 and sVEGFR1 increases tendon enthesis injury-activated SSCs better than does BMP2 alone needs further research. PURPOSE: To study the effect of BMP2 combined with sVEGFR1 on tendon-bone healing and injury-activated SSC lineage. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 128 C57BL/6 mice that underwent unilateral supraspinatus tendon detachment and repair were randomly assigned to 4 groups: (1) untreated control group; (2) hydrogel group, which received a local injection of the blank hydrogel at the injured site; (3) BMP2 group, which received an injection of hydrogel with BMP2; and (4) BMP2 with sVEGFR1 group, which received an injection of hydrogel with BMP2 and sVEGFR1. Histology, micro-computed tomography, and biomechanical tests were conducted to evaluate tendon-bone healing at 4 and 8 weeks after surgery. In addition, flow cytometry was performed to detect the proportion of SSCs and their downstream differentiated subtypes, including bone, cartilage, and stromal progenitors; osteoprogenitors; and pro-chondrogenic progenitors within supraspinatus tendon enthesis at 1 week postoperatively. RESULTS: The repaired interface in BMP2 with sVEGFR1 group showed a significantly improved collagen fiber continuity, increased fibrocartilage, greater newly formed bone, and elevated mechanical properties compared with the other 3 groups. There were more SSCs; bone, cartilage, and stromal progenitors; osteoprogenitors; and pro-chondrogenic progenitors in the BMP2 with sVEGFR1 group than that in the other groups. CONCLUSION: Our study suggests that the combined delivery of BMP2 and sVEGFR1 could promote tendon-bone healing and stimulate the expansion of SSCs and their downstream progeny within the injured tendon-bone interface. CLINICAL RELEVANCE: Combining BMP2 with sVEGFR1 may be a good clinical treatment for wounded tendon enthesis healing.

Single-cell RNA sequencing reveals cellular and molecular heterogeneity in fibrocartilaginous enthesis formation.

The attachment site of the rotator cuff (RC) is a classic fibrocartilaginous enthesis, which is the junction between bone and tendon with typical characteristics of a fibrocartilage transition zone. Enthesis development has historically been studied with lineage tracing of individual genes selected a priori, which does not allow for the determination of single-cell landscapes yielding mature cell types and tissues. Here, in together with open-source GSE182997 datasets (three samples) provided by Fang et al., we applied Single-cell RNA sequencing (scRNA-seq) to delineate the comprehensive postnatal RC enthesis growth and the temporal atlas from as early as postnatal day 1 up to postnatal week 8. And, we furtherly performed single-cell spatial transcriptomic sequencing on postnatal day 1 mouse enthesis, in order to deconvolute bone-tendon junction (BTJ) chondrocytes onto spatial spots. In summary, we deciphered the cellular heterogeneity and the molecular dynamics during fibrocartilage differentiation. Combined with current spatial transcriptomic data, our results provide a transcriptional resource that will support future investigations of enthesis development at the mechanistic level and may shed light on the strategies for enhanced RC healing outcomes.

The effect of local sympatholysis on bone-tendon interface healing in a murine rotator cuff repair model.

Background: Although neuroregulation plays an important role in tissue healing, the key neuroregulatory pathways and related neurotransmitters involved in bone-tendon interface (BTI) healing are still unknown. It is reported that sympathetic nerves can regulate cartilage and bone metabolism, which are the basic aspects of BTI repair after injury, through the release of norepinephrine (NE). Thus, the purpose of this study was to explore the effect of local sympatholysis (LS) on BTI healing in a murine rotator cuff repair model. Methods: Specifically, C57BL/6 mice underwent unilateral supraspinatus tendon (SST) detachment and repair was established on a total of 174 mature C57BL/6 mice (12 weeks old): 54 mice were used to examine the sympathetic fibers and its neurotransmitter NE for the representation of sympathetic innervation of BTI, while the rest of them were randomly allocated into (LS) group and control group to verify the effect of sympathetic denervation during BTI healing. The LS group were intervened with fibrin sealant containing 10 â€‹ng/ml guanethidine, while the control group received fibrin sealant only. Mice were euthanized at postoperative 2, 4 and 8 weeks for immunofluorescent, qRT-PCR, ELISA, Micro-computed tomography (CT), histology and biomechanical evaluations. Results: Immunofluorescence, qRT-PCR and ELISA evaluations indicated that there were the expression of tyrosine hydroxylase (TH), NE and ß2-adrenergic receptor (ß2-AR) at the BTI site. All the above showed a trend of increasing at the early postoperative stage and they started to decrease with the healing time after a significant peak. Meanwhile, local sympathetic denervation of BTI was achieved after the use of guanethidine as shown in the NE ELISA outcomes in two groups. QRT-PCR analysis revealed that the healing interface in the LS group expressed more transcription factors, such as Runx2, Bmp2, Sox9, and Aggrecan, than the control group. Further, radiographic data showed that the LS group significantly possessed higher bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and lower trabecular spacing (Tb.Sp) than the control group. Also, histological test results showed that there was more fibrocartilage regenerated at the healing interface in the LS group compared with the control group. Mechanical testing results demonstrated that the failure load, ultimate strength and stiffness in the LS group were significantly higher at postoperative week 4 (P â€‹< â€‹0.05), but not at postoperative week 8 (P â€‹> â€‹0.05), compared to the control group. Conclusion: The regulation of sympathetic innervation was involved in the healing process of injured BTI, and local sympathetic denervation by using guanethidine was beneficial for BTI healing outcomes.The translational potential of this article: This is the first study to evaluate the expression and specific role of sympathetic innervation during BTI healing. The findings of this study also imply that the antagonists of ß2-AR could serve as a potential therapeutic strategy for BTI healing. Also, we firstly successfully constructed a local sympathetic denervation mouse model by using guanethidine loaded fibrin sealant, which provided a new effective methodology for future neuroskeletal biology study.

Role of low-intensity pulsed ultrasound in regulating macrophage polarization to accelerate tendon-bone interface repair.

Low-intensity pulsed ultrasound (LIPUS) has been proven to accelerate the healing of the tendon-bone interface (TBI), and macrophages are considered to play an important regulatory role. This study was designed to explore the polarization of macrophages during treatment of TBI injury with LIPUS. In a rat model of rotator cuff tear, LIPUS or mock sonication (controls) was administered from 1 week postoperatively. The supraspinatus-supraspinatus tendon-humerus complexes were harvested for further evaluation at different time points for measures such as new bone formation, TBI maturity, ultimate failure load and stiffness, and types of macrophages. In vitro, bone marrow-derived macrophages were cultured, and polarization was identified after stimulation with or without LIPUS (the LIPUS or control groups, respectively). Two weeks posttreatment, the LIPUS group showed higher bone volume/total volume ratios and better TBI maturity scores. Six weeks posttreatment, the failure load of the LIPUS group was significantly higher than that of the control group. LIPUS also accelerated initial inflammatory macrophage accumulation and facilitated anti-inflammatory macrophage polarization (M2) in the late period. In the in vitro macrophage polarization model, the LIPUS group showed a higher proportion of M2 macrophages and mRNA expression of anti-inflammatory genes than the control group, while there was no significant difference in the proinflammatory macrophages between the two groups. Our observations revealed that macrophage polarization may be a potential mechanism of LIPUS treatment for TBI repair.

Identification of the active triple-phase boundary of a non-Pt catalyst layer in fuel cells.

The rational design of non-Pt oxygen reduction reaction (ORR) catalysts and catalyst layers in fuel cells is largely impeded by insufficient knowledge of triple-phase boundaries (TPBs) in the micropore and mesopore ranges. Here, we developed a size-sensitive molecular probe method to resolve the TPB of Fe/N/C catalyst layers in these size ranges. More than 70% of the ORR activity was found to be contributed by the 0.8- to 2.0-nanometer micropores of Fe/N/C catalysts, even at a low micropore area fraction of 29%. Acid-alkaline interactions at the catalyst-polyelectrolyte interface deactivate the active sites in mesopores and macropores, resulting in inactive TPBs, leaving micropores without the interaction as the active TPBs. The concept of active and inactive TPBs provides a previously unidentified design principle for non-Pt catalyst and catalyst layers in fuel cells.

Association Between Serum Uric Acid Levels and Suicide Attempts in Adolescents and Young Adults with Major Depressive Disorder: A Retrospective Study.

Purpose: Uric acid (UA) is thought to exert neuroprotective roles. The purpose of this study was to examine the association of serum UA with suicide attempts (SA) in adolescents and young adults with major depressive disorder (MDD). Patients and Methods: We retrospectively recruited 533 participants with MDD aged 13 to 25 years, of which 168 had a history of SA in the past three months and 365 did not have a history of SA. Serum UA levels were measured using the uricase-peroxidase coupling method. In addition to overall serum UA level comparison in MDD individuals with and without SA, a stratified analysis by biological sex was carried out. Results: Compared to MDD individuals without a history of SA, serum UA levels were significantly lower in MDD individuals with SA (P < 0.001). Female MDD, but not male MDD individuals, with SA exhibited lower levels of UA than those without SA (P < 0.01). Importantly, serum UA remained significantly associated with SA in MDD individuals (OR = 0.996, 95% CI: 0.993~0.999, P < 0.01) when controlling for possible confounding variables. Conclusion: This research identifies a relationship between serum UA levels and SA in adolescents and young adults with MDD. UA may represent a biological risk marker for SA, in particular for female MDD individuals.

High-speed railway and the intercity transmission of epidemics: Evidence from COVID-19 in China.

In the context of the COVID-19 outbreak in Wuhan, we investigate the effect of intercity high-speed railway (HSR) connections on intercity transmission of epidemics in the absence of government intervention. Intercity HSR connections increase the number of COVID-19 patients per 10,000 population by 0.029, accounting for 45% of the total infections. Our results remain intact in several robustness assessments. The total economic loss owing to HSR connections to Wuhan is estimated to be USD 0.62 billion. The internal mechanism demonstrates that intercity HSR connections increase intercity COVID-19 transmission by facilitating human mobility between cities. Based on intercity transportation connections, our findings can help the government predict the direction and scope of virus transmission and control the intercity transmission of epidemics.

Evolution of Cu single atom catalysts to nanoclusters during CO2 reduction to CO.

We synthesized Cu single atoms embedded in a N-doped porous carbon catalyst with a high Faradaic efficiency of 93.5% at -0.50 V (vs. RHE) for CO2 reduction to CO. The evolution of Cu single-atom sites to nanoclusters of about 1 nm was observed after CO2 reduction at a potential lower than -0.30 V (vs. RHE). The DFT calculation indicates that Cu nanoclusters improve the CO2 activation and the adsorption of intermediate *COOH, thus exhibiting higher catalytic activity than CuNx sites. The structural instability observed in this study helps in understanding the actual active sites of Cu single atom catalysts for CO2 reduction.

Effects of antidepressant medicines on preventing relapse of unipolar depression: a pooled analysis of parametric survival curves.

BACKGROUND: Major depressive disorder is characterized by a high risk of relapse. We aimed to compare the prophylactic effects of different antidepressant medicines (ADMs). METHODS: PubMed, Cochrane Central Register of Controlled Trials, Embase and the Web of Science were searched on 4 July 2019. A pooled analysis of parametric survival curves was performed using a Bayesian framework. The main outcomes were hazard ratios (HRs), relapse-free survival and mean relapse-free months. RESULTS: Forty randomized controlled trials were included. The 1-year relapse-free survival for ADM (76%) was significantly better than that for placebo (56%). Most of the relapse difference (86.5%) occurred in the first 6 months. Most HRs were not constant over time. Proof of benefit after 6 months of follow-up was not established partially because of small differences between the drug and placebo after 6 months. Almost all studies used an 'enriched' randomized discontinuation design, which may explain the high relapse rates in the first 6 months after randomization. CONCLUSIONS: The superiority of ADM v. placebo was mainly attributed to the difference in relapse rates that occurred in the first 6 months. Our analysis provided evidence that the prophylactic efficacy was not constant over time. A beneficial effect was observed, but the prevention of new episodes after 6 months was questionable. These findings may have implications for clinical practice.

Early treadmill running delays rotator cuff healing via Neuropeptide Y mediated inactivation of the Wnt/ß-catenin signaling.

BACKGROUND: Defining the optimal rehabilitation programs for rotator cuff healing remains a challenge. Early treadmill running may have negative effects on tendon-bone interface (TBI) healing with increased expression of Neuropeptide Y (NPY). However, the underlying mechanism is still unknown. METHODS: The mice were randomly assigned to four groups: control group, treadmill group, treadmill â€‹+ â€‹BIBO3304 group and BIBO3304 group alone. Specifically, the control group was allowed free cage activity without any treatment after surgery. The treadmill group received early treadmill running initiated from postoperative day 2. The treadmill â€‹+ â€‹BIBO3304 group received treadmill running combined with intra-articular injection of BIBO3304 postoperatively. The BIBO3304 group only received type 1 NPY receptor (Y1 receptor, Y1R) antagonist BIBO3304 postoperatively. Healing outcomes of the rotator cuff were evaluated by histological analysis, synchrotron radiation micro-computed tomography (SR-µCT) scanning, and biomechanical testing at 4 and 8 weeks after surgery. The expression of NPY and its Y1 receptor during the treadmill running were tested by immunofluorescence. In addition, the related signaling pathway of Neuropeptide Y among all groups was detected by immunohistochemistry and western-blot. RESULTS: Immunofluorescence results show that early treadmill training could lead to a significant increase in the expression of NPY at the healing site, and Y1R was widely expressed in both normal or injured rotator cuff without statistical difference. At the same time, early treadmill running delayed the healing of rotator cuff, as indicated with unsatisfactory outcomes, including a significantly lower histological score, decreased bone formation and inferior biomechanical properties at postoperative week 4 and 8. Moreover, the use of BIBO3304 could partly alleviate the negative effects of early treadmill running on the healing of rotator cuff and promote the natural healing process of rotator cuff, as evidenced by significant differences observed between the treadmill and treadmill â€‹+ â€‹BIBO3304 groups, as well as observed between the control and BIBO3304 groups. On the other hand, the expressions of Wnt3a and ß-catenin in the treadmill group were significantly lower compared with the other groups, while the expression in the BIBO3304 group was the highest, as evaluated by immunohistochemistry and western-blot. CONCLUSIONS: Early treadmill running increased the expression of NPY at the RC healing site, which might burden the expression of Wnt3a/ß-catenin and delay the healing process, inhibition of Y1 receptor with BIBO3304 could promote bone-tendon healing through the Wnt/ß-catenin signaling.The translational potential of this article: This is the first study to evaluate the specific role of the NPY-Y1R axis and its underlying mechanism by which early treadmill running delays bone-tendon healing. Further, our study may provide references of precise and individualized exercise-based rehabilitation strategies for TBI healing in clinic. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This is the first study to evaluate the specific role of the NPY-Y1R axis and its underlying mechanism by which early treadmill running delays bone-tendon healing. Further, our study may provide references of precise and individualized exercise-based rehabilitation strategies for TBI healing in clinic.

Microglia-Derived Exosomes Improve Spinal Cord Functional Recovery after Injury via Inhibiting Oxidative Stress and Promoting the Survival and Function of Endothelia Cells.

Traumatic spinal cord injury (SCI) is a devastating disease of the central nervous system with long-term disability and high mortality worldwide. Revascularization following SCI provides nutritional supports to rebuild and maintain the homeostasis of neuronal networks, and the subsequent promotion of angiogenesis is beneficial for functional recovery. Oxidative stress drastically produced following SCI has been contributed to endothelial dysfunction and the limited endogenous repair of microvasculature. Recently, exosomes, being regarded as potential therapeutic candidates for many kinds of diseases, have attracted great attentions due to its high bioavailability, safety, and stability. Microglia have been reported to exhibit proangiogenic function and guide the forming of vasculature during tissue repair. However, the specific role of microglia-derived exosomes (MG-Exos) played in SCI is still largely unknown. In the present study, we aimed to evaluate whether MG-Exos could protect spinal cord microvascular endothelial cells (SCMECs) against the toxic effects of oxidative stress, thus promote SCMECs' survival and function. We also investigated the protective effects of MG-Exos in the mouse model of SCI to verify their capability. Our results demonstrated that MG-Exo treatment significantly decreased the level of oxidative stress (ROS), as well as did the protein levels of NOX2 when bEnd.3 cells were exposed to H2O2-induced oxidative stress in vitro and in vivo. Functional assays showed that MG-Exos could improve the survival and the ability of tube formation and migration in H2O2-induced bEnd.3 in vitro. Moreover, MG-Exos exhibited the positive effects on vascular regeneration and cell proliferation, as well as functional recovery, in the mouse model of SCI. Mechanically, the keap1/Nrf2/HO-1 signaling pathway was also investigated in order to unveil its molecular mechanism, and the results showed that MG-Exos could increase the protein levels of Nrf2 and HO-1 via inhibiting the keap1; they also triggered the expression of its downstream antioxidative-related genes, such as NQo1, Gclc, Cat, and Gsx1. Our findings indicated that MG-Exos exerted an antioxidant effect and positively modulated vascular regeneration and neurological functional recovery post-SCI by activating keap1/Nrf2/HO-1 signaling.

A Mild CO2 Etching Method To Tailor the Pore Structure of Platinum-Free Oxygen Reduction Catalysts in Proton Exchange Membrane Fuel Cells.

The structural tailoring of pores is essential to high-performance Fe/N/C electrocatalysts for the oxygen reduction reaction (ORR) in proton exchange membrane fuel cells. Current strategies for pore structure engineering are usually accompanied with a drastic change of the intrinsic activity-related surface, which may mask the real effects of the porous structure on ORR activity. Herein, a mild carbon dioxide (CO2) etching method was used to flexibly tailor the pore structure of Fe/N/C electrocatalysts without drastic changes in their surface structure and property. In this way, via employing the Fe/N/C electrocatalysts as a model, the intrinsic impact of the pore structure on ORR activity was revealed. In addition, the CO2 etching method developed a high-quality electrocatalyst (sample Fe/N/C-5% CO2) with polarization performance exceeding that of the commercial Pt/C catalyst in the fuel cell working voltage region (>0.65 V). This work will promote the ongoing intensive studies on the rational design of the pore structures in the Fe/N/C electrocatalysts.

Construction of Highly Active Metal-Containing Nanoparticles and FeCo-N4 Composite Sites for the Acidic Oxygen Reduction Reaction.

Metal-containing nanoparticles (M-NPs) in metal/nitrogen-doped carbon (M-N-C) catalysts have been considered hostile to the acidic oxygen reduction reaction (ORR). The relation between M-NPs and the active sites of metal coordinated with nitrogen (MNx ) is hard to establish in acid medium owing to the poor stability of M-NPs. Herein, we develop a strategy to successfully construct a new FeCo-N-C catalyst containing highly active M-NPs and MN4 composite sites (M/FeCo-SAs-N-C). Enhanced catalytic activity and stability of M/FeCo-SAs-N-C is shown experimentally. Calculations reveal that there is a strong interaction between M-NPs and FeN4 sites, which can favor ORR by activating the O-O bond, thus facilitating a direct 4 e- process. Those findings firstly shed light on the highly active M-NPs and FeN4 composite sites for catalyzing acid oxygen reduction reaction, and the relevant reaction mechanism is suggested.

Ultrathin 2D Mesoporous TiO2 /rGO Heterostructure for High-Performance Lithium Storage.

Lithium-ion batteries (LIBs) have been widely applied and studied as an effective energy supplement for a variety of electronic devices. Titanium dioxide (TiO2 ), with a high theoretical capacity (335 mAh g-1 ) and low volume expansion ratio upon lithiation, has been considered as one of the most promising anode materials for LIBs. However, the application of TiO2 is hindered by its low electrical conductivity and slow ionic diffusion rate. Herein, a 2D ultrathin mesoporous TiO2 /reduced graphene (rGO) heterostructure is fabricated via a layer-by-layer assembly process. The synergistic effect of ultrathin mesoporous TiO2 and the rGO nanosheets significantly enhances the ionic diffusion and electron conductivity of the composite. The introduced 2D mesoporous heterostructure delivers a significantly improved capacity of 350 mAh g-1 at a current density of 200 mA g-1 and excellent cycling stability, with a capacity of 245 mAh g-1 maintained over 1000 cycles at a high current density of 1 A g-1 . The in situ transmission electron microscopy analysis indicates that the volume of the as-prepared 2D heterostructures changes slightly upon the insertion and extraction of Li+ , thus contributing to the enhanced long-cycle performance.

Porous Carbon Membrane-Supported Atomically Dispersed Pyrrole-Type FeN4 as Active Sites for Electrochemical Hydrazine Oxidation Reaction.

The rational design of catalytically active sites in porous materials is essential in electrocatalysis. Herein, atomically dispersed Fe-Nx sites supported by hierarchically porous carbon membranes are designed to electrocatalyze the hydrazine oxidation reaction (HzOR), one of the key techniques in electrochemical nitrogen transformation. The high intrinsic catalytic activity of the Fe-Nx single-atom catalyst together with the uniquely mixed micro-/macroporous membrane support positions such an electrode among the best-known heteroatom-based carbon anodes for hydrazine fuel cells. Combined with advanced characterization techniques, electrochemical probe experiments, and density functional theory calculation, the pyrrole-type FeN4 structure is identified as the real catalytic site in HzOR.

Hierarchically Porous Carbons Derived from Nonporous Coordination Polymers.

Hierarchically porous carbons (HPCs) with multimodal pore systems exhibit great technological potentials, especially in the fields of heterogeneous catalysis, energy storage, and conversion. Here, we establish a simple and general approach to HPCs by carbonization of nonporous coordination polymers that are produced by mixing metal salts with polytopic ligands in alkaline aqueous solutions at room temperature. The proposed approach is applicable to a wide scope of ligand molecules (18 examples), thus affording the synthesized HPCs with high diversity in porosity, morphology, and composition. In particular, the prepared HPCs exhibit high specific surface areas (up to 2647 m2 g-1) and large pore volumes (up to 2.39 cm3 g-1). The HPCs-supported atomically dispersed Fe-Nx catalysts show much-improved fuel cell cathode performance over the micropore-dominated carbon black-supported catalysts, demonstrating the structural superiority of the HPCs for enhancing the mass transport properties.

KOH-doped polybenzimidazole membrane for direct hydrazine fuel cell.

Alkaline direct hydrazine (N2H4) fuel cells (DHFCs) are considered one of the most promising liquid-fed fuel cells because of their high energy density, high theoretical voltage, and zero carbon dioxide (CO2) emissions. However, the lack of a suitable electrolyte membrane impedes the further development of alkaline DHFC. Herein, a potassium hydroxide (KOH)-doped polybenzimidazole (PBI) membrane is applied in alkaline DHFCs, and the detailed operating conditions are investigated for the first time. With optimal KOH and N2H4 concentrations in the anolyte, membrane thickness, and cathode gas humidity, the DHFC gives a peak power density of 0.708 W cm-2. The results of this study demonstrate the promising application of PBI membranes in DHFC and provide a platform to evaluate the performance of catalysts synthesized for DHFC.

Augmentation agents to serotonin reuptake inhibitors for treatment-resistant obsessive-compulsive disorder: A network meta-analysis.

BACKGROUND: Various agents for augmentation of serotonin reuptake inhibitors have been investigated for treatment-resistant obsessive-compulsive disorder (OCD). We aimed to comprehensively compare different augmentation agents for treatment-resistant OCD in adults. METHODS: PubMed, Embase, Web of Science, CENTRAL, the WHO's ICTRP, and ClinicalTrials.gov were searched on February 20, 2018. Pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcome was efficacy measured by the Yale-Brown Obsessive Compulsive Scale. The secondary outcomes were tolerability (side-effect discontinuation) and acceptability (all cause discontinuation). Mean differences (MDs) and odds ratios (ORs) were reported with 95% confidence intervals (CIs). RESULTS: Thirty-three articles with 34 trials (1216 patients) were included. Memantine (MD, -8.94; 95% CI, -14.42 to -3.42), risperidone (-4.47, -8.75 to -0.17), topiramate (-6.05, -10.89 to -1.20), lamotrigine (-6.07, -11.61 to -0.50), and aripiprazole (-5.14, -9.95 to -0.28) were significantly superior to placebo. Antipsychotic (-4.09, -6.22 to -1.93) and glutamatergic (-5.22, -7.53 to -2.84) agents were significantly superior to placebo. Considerable heterogeneity was found across studies, and baseline symptom severity was identified as a significant moderator. After baseline severity adjustment, quetiapine (-5.00, -8.59 to -1.29) and olanzapine (-8.28, -15.34 to -1.13) became significantly superior to placebo. CONCLUSIONS: Our study supports the use of antipsychotic or glutamatergic agents as augmentation agents for treatment-resistant OCD. Topiramate, lamotrigine, aripiprazole, olanzapine, risperidone, memantine, and quetiapine are alternative augmentation drugs; however, a definitive conclusion of the best drug remains undetermined because of the considerable heterogeneity and limited numbers of studies and patients for each agent.

[Experimental research of hot alkaline solution etching treatment on zirconia/resin bonding strength].

PURPOSE: In this experiment, we applied hot alkaline solution (20%NaOH solutions) to treat the surfaces of zirconia ceramics in vitro, then evaluated the changes of bond strength of zirconia ceramics and resin cement. METHODS: Eighteen pieces of zirconia ceramic specimens were made, using the same method of grinding and polishing, and then randomly divided them into 3 groups: group A with hot alkali solution treatment (20%NaOH) (n=6), group B underwent sand blasting with a diameter of 110 ?m alumina particles (n=6), group C was as the control group. Atomic force microscope was used to measure the roughness of the surface of the specimens, and the zirconia surfaces were scanned to get topography maps, then made them into ceramic/resin-bonded specimens. After 24 h of water reservoir processing, shearing bonding strength (SBS) test was conducted and their bond interfaces were observed to investigate the lesions of different degree in these specimens. The data were analyzed with SPSS20.0 software package. RESULTS: Surface roughness was group B> group A > group C, SBS was group B>group A>group C. CONCLUSIONS: Under the condition of 180degrees centigrade, bonding strength between zirconia and resin cement after treatment with 20% NaOH solution was significantly higher than without any treatment, but lower than sand blasting treatment.

Short-Lived Buildings in China: Impacts on Water, Energy, and Carbon Emissions.

This paper has changed the vague understanding that "the short-lived buildings have huge environmental footprints (EF)" into a concrete one. By estimating the annual floor space of buildings demolished and calibrating the average building lifetime in China, this paper compared the EF under various assumptive extended buildings' lifetime scenarios based on time-series environmental-extended input-output model. Results show that if the average buildings' lifetime in China can be extended from the current 23.2 years to their designed life expectancy, 50 years, in 2011, China can reduce 5.8 Gt of water withdrawal, 127.1 Mtce of energy consumption, and 426.0 Mt of carbon emissions, each of which is equivalent to the corresponding annual EF of Belgium, Mexico, and Italy. These findings will urge China to extend the lifetime of existing and new buildings, in order to reduce the EF from further urbanization. This paper also verifies that the lifetime of a product or the replacement rate of a sector is a very important factor that influences the cumulative EF. When making policies to reduce the EF, adjusting people's behaviors to extend the lifetime of products or reduce the replacement rate of sectors may be a very simple and cost-effective option.